MCP1 SNPs and Pulmonary Tuberculosis in Cohorts from West Africa, the USA and Argentina: Lack of Association or Epistasis with IL12B Polymorphisms

The monocyte chemotactic protein-1 (MCP-1) is a chemokine that plays an important role in the recruitment of monocytes to M. tuberculosis infection sites, and previous studies have reported that genetic variants in MCP1 are associated with differential susceptibility to pulmonary tuberculosis (PTB). We examined eight MCP1 single nucleotide polymorphisms (SNPs) in a multi-ethnic, case-control design that included: 321 cases and 346 controls from Guinea-Bissau, 258 cases and 271 controls from The Gambia, 295 cases and 179 controls from the U.S. (African-Americans), and an additional set of 237 cases and 144 controls of European ancestry from the U.S. and Argentina. Two locus interactions were also examined for polymorphisms in MCP1 and interleukin 12B (IL12B), another gene implicated in PTB risk. Examination of previously associated MCP1 SNPs rs1024611 (−2581A/G), rs2857656 (−362G/C) and rs4586 (+900C/T) did not show evidence for association. One interaction between rs2857656 and IL12B SNP rs2288831 was observed among Africans but the effect was in the opposite direction in Guineans (OR = 1.90, p = 0.001) and Gambians (OR = 0.64, p = 0.024). Our data indicate that the effect of genetic variation within MCP1 is not clear cut and additional studies will be needed to elucidate its role in TB susceptibility

Emissões públicas de ações, volatilidade e insider information na Bovespa

O trabalho utiliza um estudo de evento para examinar os retornos de ações relacionados a emissões públicas por empresas brasileiras listadas na BOVESPA, realizadas entre 1992 e 2002, buscando determinar como o mercado reagiu antes, durante e depois da data do anúncio da emissão. Após utilizar a metodologia convencional de mensuração de retornos anormais por OLS, foram utilizados modelos ARCH e GARCH, que levam em consideração a heteroscedasticidade condicional da volatilidade dos retornos anormais, em mais de 70% da amostra, após a constatação da presença desses processos nos resíduos originais. Os resultados mostram que 1) há evidências de insider information antes da data do anúncio, (2) que ocorrem retornos anormais negativos na data do anúncio e (3) que, no período de um ano após as emissões, as ações das empresas que captaram recursos via underwriting tiveram retornos negativos após ajuste ao risco e ao mercado

Genome-Wide Association Meta-analysis of Neuropathologic Features of Alzheimer's Disease and Related Dementias

Alzheimer's disease (AD) and related dementias are a major public health challenge and present a therapeutic imperative for which we need additional insight into molecular pathogenesis. We performed a genome-wide association study and analysis of known genetic risk loci for AD dementia using neuropathologic data from 4,914 brain autopsies. Neuropathologic data were used to define clinico-pathologic AD dementia or controls, assess core neuropathologic features of AD (neuritic plaques, NPs; neurofibrillary tangles, NFTs), and evaluate commonly co-morbid neuropathologic changes: cerebral amyloid angiopathy (CAA), Lewy body disease (LBD), hippocampal sclerosis of the elderly (HS), and vascular brain injury (VBI). Genome-wide significance was observed for clinico-pathologic AD dementia, NPs, NFTs, CAA, and LBD with a number of variants in and around the apolipoprotein E gene (APOE). GalNAc transferase 7 (GALNT7), ATP-Binding Cassette, Sub-Family G (WHITE), Member 1 (ABCG1), and an intergenic region on chromosome 9 were associated with NP score; and Potassium Large Conductance Calcium-Activated Channel, Subfamily M, Beta Member 2 (KCNMB2) was strongly associated with HS. Twelve of the 21 non-APOE genetic risk loci for clinically-defined AD dementia were confirmed in our clinico-pathologic sample: CR1, BIN1, CLU, MS4A6A, PICALM, ABCA7, CD33, PTK2B, SORL1, MEF2C, ZCWPW1, and CASS4 with 9 of these 12 loci showing larger odds ratio in the clinico-pathologic sample. Correlation of effect sizes for risk of AD dementia with effect size for NFTs or NPs showed positive correlation, while those for risk of VBI showed a moderate negative correlation. The other co-morbid neuropathologic features showed only nominal association with the known AD loci. Our results discovered new genetic associations with specific neuropathologic features and aligned known genetic risk for AD dementia with specific neuropathologic changes in the largest brain autopsy study of AD and related dementias

Determinants of countermovement jump performance: a kinetic and kinematic analysis

This is an Accepted Manuscript of an article published in Journal of Sports Sciences on 29 May 2014, available online: http://www.tandfonline.com/10.1080/02640414.2014.924055This study aimed to investigate the contributions of kinetic and kinematic parameters to inter-individual variation in countermovement jump (CMJ) performance. Two-dimensional kinematic data and ground reaction forces during a CMJ were recorded for 18 males of varying jumping experience. Ten kinetic and eight kinematic parameters were determined for each performance, describing peak lower-limb joint torques and powers, concentric knee extension rate of torque development and CMJ technique. Participants also completed a series of isometric knee extensions to measure the rate of torque development and peak torque. CMJ height ranged from 0.38 to 0.73 m (mean 0.55 ± 0.09 m). CMJ peak knee power, peak ankle power and take-off shoulder angle explained 74% of this observed variation. CMJ kinematic (58%) and CMJ kinetic (57%) parameters explained a much larger proportion of the jump height variation than the isometric parameters (18%), suggesting that coachable technique factors and the joint kinetics during the jump are important determinants of CMJ performance. Technique, specifically greater ankle plantar-flexion and shoulder flexion at take-off (together explaining 58% of the CMJ height variation), likely influences the extent to which maximal muscle capabilities can be utilised during the jump

Baseline spatial distribution of malaria prior to an elimination programme in Vanuatu

BACKGROUND: The Ministry of Health in the Republic of Vanuatu has implemented a malaria elimination programme in Tafea Province, the most southern and eastern limit of malaria transmission in the South West Pacific. Tafea Province is comprised of five islands with malaria elimination achieved on one of these islands (Aneityum) in 1998. The current study aimed to establish the baseline distribution of malaria on the most malarious of the province's islands, Tanna Island, to guide the implementation of elimination activities. METHODS: A parasitological survey was conducted in Tafea Province in 2008. On Tanna Island there were 4,716 participants from 220 villages, geo-referenced using a global position system. Spatial autocorrelation in observed prevalence values was assessed using a semivariogram. Backwards step-wise regression analysis was conducted to determine the inclusion of environmental and climatic variables into a prediction model. The Bayesian geostatistical logistic regression model was used to predict malaria risk, and associated uncertainty across the island. RESULTS: Overall, prevalence on Tanna was 1.0% for Plasmodium falciparum (accounting for 32% of infections) and 2.2% for Plasmodium vivax (accounting for 68% of infections). Regression analysis showed significant association with elevation and distance to coastline for P. vivax and P. falciparum, but no significant association with NDVI or TIR. Colinearity was observed between elevation and distance to coastline with the later variable included in the final Bayesian geostatistical model for P. vivax and the former included in the final model for P. falciparum. Model validation statistics revealed that the final Bayesian geostatistical model had good predictive ability. CONCLUSION: Malaria in Tanna Island, Vanuatu, has a focal and predominantly coastal distribution. As Vanuatu refines its elimination strategy, malaria risk maps represent an invaluable resource in the strategic planning of all levels of malaria interventions for the island

Potential impact of invasive alien species on ecosystem services provided by a tropical forested ecosystem: a case study from Montserrat

Local stakeholders at the important but vulnerable Centre Hills on Montserrat consider that the continued presence of feral livestock (particularly goats and pigs) may lead to widespread replacement of the reserve’s native vegetation by invasive alien trees (Java plum and guava), and consequent negative impacts on native animal species. Since 2009, a hunting programme to control the feral livestock has been in operation. However long-term funding is not assured. Here, we estimate the effect of feral livestock control on ecosystem services provided by the forest to evaluate whether the biodiversity conservation rationale for continuation of the control programme is supported by an economic case. A new practical tool (Toolkit for Ecosystem Service Site-based Assessment) was employed to measure and compare ecosystem service provision between two states of the reserve (i.e. presence and absence of feral livestock control) to estimate the net consequences of the hunting programme on ecosystem services provided by the forest. Based on this we estimate that cessation of feral livestock management would substantially reduce the net benefits provided by the site, including a 46 % reduction in nature-based tourism (from $419,000 to$228,000) and 36 % reduction in harvested wild meat (from $205,000 to$132,000). The overall net benefit generated from annual ecosystem service flows associated with livestock control in thereserve, minus the management cost, was $214,000 per year. We conclude that continued feral livestock control is important for maintaining the current level of ecosystem services provided by the reserve

Large Scale Comparison of Innate Responses to Viral and Bacterial Pathogens in Mouse and Macaque

Viral and bacterial infections of the lower respiratory tract are major causes of morbidity and mortality worldwide. Alveolar macrophages line the alveolar spaces and are the first cells of the immune system to respond to invading pathogens. To determine the similarities and differences between the responses of mice and macaques to invading pathogens we profiled alveolar macrophages from these species following infection with two viral (PR8 and Fuj/02 influenza A) and two bacterial (Mycobacterium tuberculosis and Francisella tularensis Schu S4) pathogens. Cells were collected at 6 time points following each infection and expression profiles were compared across and between species. Our analyses identified a core set of genes, activated in both species and across all pathogens that were predominantly part of the interferon response pathway. In addition, we identified similarities across species in the way innate immune cells respond to lethal versus non-lethal pathogens. On the other hand we also found several species and pathogen specific response patterns. These results provide new insights into mechanisms by which the innate immune system responds to, and interacts with, invading pathogens

Thermostable DNA Polymerase from a Viral Metagenome Is a Potent RT-PCR Enzyme

Viral metagenomic libraries are a promising but previously untapped source of new reagent enzymes. Deep sequencing and functional screening of viral metagenomic DNA from a near-boiling thermal pool identified clones expressing thermostable DNA polymerase (Pol) activity. Among these, 3173 Pol demonstrated both high thermostability and innate reverse transcriptase (RT) activity. We describe the biochemistry of 3173 Pol and report its use in single-enzyme reverse transcription PCR (RT-PCR). Wild-type 3173 Pol contains a proofreading 3′-5′ exonuclease domain that confers high fidelity in PCR. An easier-to-use exonuclease-deficient derivative was incorporated into a PyroScript RT-PCR master mix and compared to one-enzyme (Tth) and two-enzyme (MMLV RT/Taq) RT-PCR systems for quantitative detection of MS2 RNA, influenza A RNA, and mRNA targets. Specificity and sensitivity of 3173 Pol-based RT-PCR were higher than Tth Pol and comparable to three common two-enzyme systems. The performance and simplified set-up make this enzyme a potential alternative for research and molecular diagnostics